Abstract Purpose: The long-term goal of this research is to devise a non-invasive method to accurately assess 3-D in vivo spine kinematics to facilitate clinical studies aimed at improving diagnosis and assessment of treatments for degenerative spine conditions. Hypotheses: Our central hypothesis is that a patient-specific, MRI-based technique can be developed to accurately quantify continuous 3-D vertebral motions, facet joint motions, and spinal canal and foraminal stenosis utilizing tools that could be readily available to clinicians, and without excessive radiation exposure. The above hypothesis is based on our prior work in the laboratory, which has led to the development of a specimen-specific, 3-D kinematic assessment tool for human cadaveric studies of reconstructive surgeries. Specific Aims: (1) Development and ex vivo validation of a non-invasive, bi-planar fluoroscopic imaging technique for registration of vertebral anatomy. Working hypothesis 1: A bi-planar fluoroscopic registration method can be devised that, in conjunction with a 3-D MRI anatomic model, can accurately assess segmental kinematics at discrete positions as accurately as the laboratory technique that utilizes radiopaque spheres implanted on each vertebra. (2) Development and ex vivo validation of an algorithm for prediction of continuous kinematic data from segmental motions measured in discrete postures. Working hypothesis 2: Interpolation using 3-D spline functions can create an accurate prediction of continuous kinematic data based upon the bi-planar fluoroscopic data obtained for discrete positions. Research Plan: We will use a combination of experimental studies on human cadaveric spines, CT- and MRI- based anatomic models and bi-planar fluoroscopic imaging to develop a non-invasive method to acquire continuous 3-D kinematic data as specified in the aims of the proposed study. Our overall approach is illustrated in a flowchart. The first steps of the study are to: (1) design/refine an algorithm for registration of vertebral anatomy using bi-planar fluoroscopic imaging; and (2) design/refine an interpolation algorithm to predict continuous data from vertebral motion data acquired at discrete positions. These algorithms will be implemented on experimental data collected on human cadaveric spine specimens. The cadaveric experiments will simultaneously yield: (i) Gold Standard continuous kinematic data that is obtained using radiopaque spheres implanted on vertebral bodies, and an optoelectronic tracking system consisting of infrared light emitting diodes attached to each vertebra and IRED tracking cameras, and (ii) kinematic data derived from the proposed bi-planar registration technique in conjunction with an interpolation algorithm to derive continuous data. We will use the experimental data collected above to build and compare 3 specimen-specific models: (1) a CT-based gold standard model, (2) a CT-based model using bi-planar fluoroscopic image registration, and (3) an MRI-based model using bi-planar fluoroscopic image registration. Kinematic parameters calculated from the 3-D data will yield information on the accuracy and precision of the proposed non-invasive techniques. Significance: The contributions of the proposed study will include: (1) a robust, non-invasive kinematic assessment procedure utilizing tools that could be readily available to clinicians; and (2) a non-invasive method to acquire continuous 3-D kinematic data without excessive radiation; which in conjunction with the patient's 3-D anatomic model will allow dynamic assessment of axes of rotation, facet joint motions, spinal canal and foraminal stenosis, and in vivo 3-D disc deformations under functional loading scenarios.